Definition and Pathogenesis

Obsessive-compulsive disorder is characterised by recurrent, intrusive and distressing thoughts, ideas or images (obsessions) that drive the patient to perform repetitive, ritualistic mental or physical acts (compulsions) in an attempt to prevent or reduce stress.^{3, 4, 5}

The exact aetiology of OCD is unknown, but research suggests that multiple genetic risk factors leading to altered neurotransmitter signaling or changes in cellular function that perturb fronto-striatal-thalamic circuitry (FSTC), may be associated with OCD.⁶ Abnormalities in serotonin (5-HT) neurotransmission have been implicated and this possible aetiology is strongly supported by the efficacy of serotonin reuptake inhibitors in the treatment of OCD.⁴ Other metabolites along with serotonin that may also be involved in neurochemistry of OCD include N-acetyl-aspartate, choline and creatinine/phosphocreatine.⁶ Abnormalities in dopaminergic transmission have been implicated in at least some patients with OCD.⁴ Attention has recently focused on glutamatergic abnormalities (with involvement of the neurotransmitters glutamate and gamma-aminobutyric acid (GABA)) and possible glutamatergic treatments for OCD.⁴

Orbitofrontal-subcortical circuitry mediates strong emotions and the autonomic responses to those emotions. Research suggests that the symptoms of OCD are driven by impairment of intracortical inhibition of this circuit. Neurosurgical intervention called cingulotomy, interrupts this circuit and is sometimes used for severe and treatment-resistant OCD.⁴

Twin and family studies provide compelling evidence of critical involvement of genetic factors, and a possible link to a region on chromosome 9.⁶ A variety of serotonergic, dopaminergic and glutamatergic genes are also linked to OCD.⁴ Infectious diseases have been reported as precipitating factors of OCD, especially group A beta-haemolytic streptococcus (GABHS). There have also been some reports of OCD after herpes simplex infections.^{4, 6} It is thought
that these infections trigger a central nervous system autoimmune response that results in basal ganglia inflammation and neuropsychiatric symptoms including OCD (paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections or PANDAS).^{4, 6} There are reports of improvement in symptoms after antibiotic treatment.⁴ Other factors that can precipitate or increase the risk of OCD include premenstrual and postpartum periods (hormonal fluctuations), perinatal complications, stress, brain trauma, stimulant abuse and carbon monoxide poisoning.^{4, 6, 7}

Diagnosis and Rating Scales

The diagnosis of OCD is based on criteria as set out by DSM-5.^{1,4 6}

A. Presence of obsessions and/or compulsions.

Obsessions are defined as:

• Recurrent and persistent thoughts, impulses, or images that are experienced at some time during the disturbance, as intrusive and inappropriate, and that cause marked anxiety or distress.
• The individual attempts to ignore or suppress such thoughts, impulses, or images, or tries to neutralise them with some other thought or action (i.e. by performing a compulsion).

Compulsions are defined as:

• Repetitive behaviours (e.g. hand washing, ordering, checking) or mental acts (e.g. praying, counting, repeating words silently) that the individual feels driven to perform in response to an obsession, or according to rules that must be applied rigidly.
• The behaviours or mental acts are aimed at preventing or reducing anxiety or distress or preventing some dreaded event or situation. However, these behaviours or mental acts are either not connected in a realistic way with what they are designed to neutralise or prevent, or are excessive.

B. At some point during the course of the disorder, the person recognises that the obsessions or compulsions are excessive or unreasonable. (This is not applicable for children.)

C. The obsessions or compulsions are time-consuming (take more than 1 hour per day) or cause marked distress or impairment in social, occupational (academic), or other important areas of functioning.

D. The obsessive-compulsive symptoms are not attributable to the physiological effects of a substance (e.g. a drug of abuse, a medication) or another medical condition.

E. The disturbance is not better explained by the symptoms of another mental disorder such as:

• Obsessive-compulsive personality disorder
• Other mood and anxiety disorders with excessive worries or preoccupation with illness (generalised anxiety disorder or illness anxiety disorder)
• Suicidal thoughts and behaviours
• Ritualised eating behaviour as in eating disorders
• Preoccupation with substances or gambling (addiction or substance-related disorders)
• Sexual urges or fantasies as in paraphilic disorders
• Stereotypes as in stereotypic movement disorder
• Repetitive behaviour as in autism spectrum disorder
• Thought insertion or delusional preoccupations as in schizophrenia or other psychotic disorders
• Attention deficit-hyperactivity disorder (ADHD)
• Tic disorder
• Somatoform disorders (hypochondriasis and BDD)
• Impulse control disorders (kleptomania and TTM)

Hoarding disorder (HD), body dysmorphic disorder (BDD), trichotillomania (TTM) and excoriation (skin picking disorder - SPD) display enough similarities in terms of obsessive pre-occupation and repetitive behaviours to be included as OCD-related disorders, but enough important differences to exist as distinct disorders.²

A number of valid rating scales are available to assess the presence of obsessive and compulsive symptoms and their severity.⁸ In addition, these rating scales are useful to monitor treatment course and response. Rating scales are available as clinician-administered interviews or patient reports.⁸ Assessments from multiple informants including clinicians, patients and significant others are likely to be most informative.⁸

Some of the scales used to establish primary, co-morbid and differential diagnoses in adults with OCD and other psychiatric conditions include the Anxiety Disorders Interview Schedule (ADIS) and Structured Clinical Interview for DSM-IV Axis I Disorders.⁸ Several other scales, specific to OCD, have been used to measure symptom severity.⁸ Clinician administered scales include Y-BOCS (Yale-Brown Obsessive Compulsive Scale), the improved Y-BOCS-11 scales and the NIMH-GOCS (National Institute of Mental Health Global Obsessive Compulsive Rating Scale).⁸ Despite some shortcomings, the Y-BOCS scale is considered the gold standard in assessing the presence and severity of obsessive-compulsive symptoms.⁸ It consists of two basic sections - a symptom checklist that assesses the presence of 64 obsessions and compulsions and a severity scale with three primary severity scale scores - one for obsessions (range 0-20), one for compulsions (range 0-20) and a total score (range 0-40).⁸

Some self-reporting scales that are used include the Y-BOCS-Self Report (Y-BOCS-SR), the widely used Obsessive-Compulsive Inventory-Revised (OCI-R) and the Florida Obsessive Compulsive Inventory (FOCl).⁸

In order to have a consistent format for rating of severity of symptoms, a working group has developed scales for BDD, HD, TTM and SPD in DSM-5.⁹ If these scales are further validated by future research and incorporated into clinical and research assessments, they have the potential to serve as a standardised method to determine disorder severity, subthreshold symptom presentations and changes in severity over time.⁹

In addition to psychiatric assessments, clinicians should also undertake a comprehensive medical history and physical examination to rule out other medical or neurological conditions as a possible cause of OCD symptoms.⁶

Clinical presentation and impact

Although the content of obsessions and compulsions vary widely among individuals, there are certain identifiable themes called "symptom dimensions".⁷ These themes include cleaning, symmetry, forbidden or taboo thoughts (i.e. sexual or religious obsession) and harm.⁷ Patients often have symptoms in multiple dimensions.⁷

These obsessions and compulsions are intrusive, unwanted, not pleasurable and time-consuming, causing marked distress, anxiety or disgust in most individuals.^1,6,7 Patients typically have little or no control over these obsessions and compulsions.⁵ Onset of symptoms is usually gradual, but acute onset has been reported after infections.⁷ If untreated, OCD is usually chronic with waxing and waning of symptoms.⁷ Treatment in adults may lead to remission in around 25-58% of patients while up to 40% with childhood or adolescent onset may achieve remission by early adulthood.⁷ Remission is defined as experiencing only mild symptoms.⁷ Over time, around 15% of patients may experience worsening of symptoms or deterioration in functioning.⁴ Adults often have insight into the excessiveness or absurdity of symptoms, but younger children may be unable to describe obsessive thoughts or their aim in carrying out a compulsive action, which makes it more difficult to identify in this population.⁶

Some patients may also present with skin conditions such as eczematous eruptions due to excessive washing, bald patches or hair loss due to trichotillomania and excoriations related to compulsive skin picking or neurodermatitis.⁴

OCD can lead to occupational, academic and social impairment and has a negative impact on quality of life.⁷ Patients often avoid situations that can trigger obsessions or compulsions and this can severely restrict functioning.⁷ Persons with OCD may also try to impose rules and prohibitions on their family members. Accommodation of these rules and participation in the rituals are often associated with high expressed emotion that can result in poor treatment response, high family burden and poor quality of life among family members living with a person suffering from OCD.⁷

Co-morbidities in the OCD patient

Patients with OCD often suffer from other psychiatric conditions.⁶ OCD is much more common in individuals with schizophrenia or schizoaffective disorder, bipolar disorder, eating disorders and Tourette's syndrome. Patients diagnosed with these conditions should also be assessed for OCD.⁷

More than half of children suffering from OCD also suffer from at least one other psychiatric condition which can include an anxiety disorder, mood disorder, eating disorder, Tourette's syndrome, disruptive behaviour disorder, speech or development disorder, enuresis and pervasive developmental disorder.⁶ Children with an early age onset of OCD are more likely to also suffer from attention deficit hyperactivity disorder and non-OCD anxiety disorders.⁶

Treatment
General treatment considerations
In order to achieve optimal management of OCD, it is important that the clinician forms a strong therapeutic alliance with the patient.¹¹ It may be necessary to adapt communication styles to suit the patient.¹¹ Since patients with OCD are often excessively doubtful, it may be useful to repeat explanations and give patients sufficient time to consider treatment options before making decisions.¹¹ It is also important to involve significant others such as family or household members or schools and liaise with other healthcare professionals to obtain as much information as possible and monitor progress.¹¹

Patients should be assessed for the risk of self-harm, including suicide and should be questioned about previous aggressive behaviour to ensure the safety of patients and those around them.¹¹ Although adult patients with OCD are at higher risk of committing suicide, this does not seem to be the case in children with OCD.⁶ However, depression, often a co-morbid condition with OCD, is associated with an increased risk of suicide.⁶ It is important to ensure that the effects of the disorder on patient's children be diminished by working with the unaffected parent.¹¹

Educating the patient and family on the disorder, its treatment and side-effects that may be expected, is imperative to enhance patient compliance.^1,11 Patients should be informed that it may take time to see an improvement.¹ Realistic goals in terms of reducing symptom frequency and severity should be set with the patient to improve functionality and quality of life.^1,11 When deciding on treatment, it is important to consider factors such as accessibility to psychotherapy, patient preference and other patient factors such as co-morbid conditions, possible medicine interactions, pregnancy and lactation.¹¹

Non-pharmacological treatment
For most patients with OCD, exposure and response prevention (a type of cognitive behavioural therapy) can be considered as first-line treatment and the psychotherapy of choice for paediatric OCD is cognitive behavioural therapy (CBT).^3,5 For mild OCD in pregnant and postpartum women without immediate risks to the mother or child, treatment with CBT may be used.¹⁰ The number and duration of treatment sessions vary across studies, but some guidelines recommend 13-20 weekly sessions for most patients.¹ CBT can be delivered as group, individual or family therapy formats.¹ Adjunctive attachment therapy may be useful for parents with OCD if bonding or an attachment issue is present after birth.¹⁰ In adults, the dose and timing of combining pharmacotherapy and CBT seems to influence the efficacy of the combination. The combination seems to be more effective when CBT treatment is given at less frequent intervals and if it is started after stabilisation with a selective serotonin reuptake inhibitor (SSRI).³

CBT treatment for OCD in children requires involvement of the parents and is delivered in five phases of treatment:⁵
1. Psychoeducation
2. Cognitive training
3. Mapping OCD
4. Graded exposure and response prevention
5. Relapse prevention and generalisation training

Individual sessions are preferred for children with or without the presence of parents, but group sessions have also been shown to be effective. The clinical effects of CBT decline over time and booster sessions over the months or years following CBT may prevent or reverse this decline.⁵

Pharmacotherapy
Selective serotonin reuptake inhibitors (SSRIs) and the tricyclic antidepressant, clomipramine are equally effective in the treatment of OCD.³ The incidence of adverse effects is lower with the use of SSRIs than treatment with clomipramine and therefore it seems reasonable to suggest SSRIs as a first-line treatment option when pharmacotherapy is indicated.¹ SSRIs that are effective for treatment of OCD in adults include citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline.³ All the SSRIs appear to be similarly effective and the choice will depend on patient factors as mentioned above, side-effect profile and past treatment history.¹

Initially, SSRIs should be used at low doses, especially in patients with co-morbid panic disorder.¹ The dose can be increased weekly or every 2 weeks, as tolerated, and should be maintained within the therapeutic range for at least 6 weeks.³ An adequate treatment trial is considered as the maximum tolerated dose of the SSRI for a minimum of 6 weeks.³ Table 2 provides a summary of dosing recommendations for medications to treat OCD.¹²

Increasing the doses of SSRIs to higher doses than recommended may be effective for some patients with OCD, but is not an effective strategy for all patients and can lead to more side-effects.³ Most patients may see improvement after 4-6 weeks of treatment, but it may take up to 8-10 or even 12 weeks for other patients to experience any improvement.¹ Patients who respond to treatment, should continue treatment for at least 1-2 years to prevent relapse. However, this needs further study. Thereafter an attempt can be made to discontinue treatment.³ Medications should be tapered off slowly, e.g. reducing the dose by 10-25% every 1-2 months.^1,3

Higher doses of venlafaxine, a serotonin-noradrenaline reuptake inhibitor (SNRI), were found to have an efficacy similar to the SSRIs and clomipramine in treating symptoms of OCD, but larger placebo-controlled trials are needed. A case series reported a reduction in OCD symptoms with duloxetine (up to 120 mg per day) in three out of four patients who did not respond to SSRIs or clomipramine.³

Due to the risk of QTc interval prolongation, the use of citalopram at doses higher than 40 mg per day is no longer recommended by The Food and Drug Administration (FDA).³

Dosing with SSRIs in children should start at low doses and then be uptitrated gradually every 2-4 weeks to reach the therapeutic dose. Treatment should be continued for a 12 week trial. ⁵ A further treatment period of gradual adjustments, for another 6-12 weeks can be added, if response is inadequate. ⁵

Although it is best to avoid pharmacotherapy during pregnancy, patients with moderate to severe OCD may need treatment with a serotoninergic antidepressant.¹ Consultation with a specialist in this area is recommended. There seems to be growing literature pointing towards the relative safety of fluoxetine during pregnancy.¹ The benefits and risks of treatment should be carefully considered against the potential risks of untreated illness. Both the patient and her partner should be part of an informed decision-making process and should provide consent for treatment.¹⁰

Managing refractory cases

In patients with partial or no response to treatment after completion of an optimal trial of medication, it may be worthwhile to check on the presence of other factors that may negatively impact treatment. These include: ^{1, 7, 11}

• Checking patient compliance with the patient or family.
• Questioning patients about the presence of adverse effects, especially those that patients may refrain from mentioning, such as sexual dysfunction, which may lead to poor patient compliance.
• Exclude poor compliance due to concern about addiction or using medication as a "crutch".
• Sometimes the fear that medication is contaminated may prevent successful treatment of OCD.
• Investigate and exclude any underlying medical conditions.
• Pharmacological interactions may lead to sub-therapeutic levels or toxicity.
• Co-morbid substance use should also be assessed, and where necessary, there may be a need for withdrawal before tackling the OCD per se.
• Families that accommodate the obsessive-compulsive rituals of the patient may derail treatment.

Once all factors contributing to a suboptimal response have been addressed and an optimal medication trial still does not result in satisfactory response, further steps and adjustments to medication may be considered.¹

If a trial of a SSRI or SNRI results in a partial response, but the patient continues to experience clinically significant symptoms, the antidepressant treatment may be augmented with CBT before trying antipsychotic medication.³ Patients can first try treatment with both pharmacotherapy as well as CBT or increase intensity of the CBT.^{1, 11} CBT may also reduce the risk of relapse once pharmacotherapy is discontinued.^{1, 11} Adding an antipsychotic such as risperidone or haloperidol to a SSRI may improve response rate in up to one-half of refractory cases.¹ If there is no clear improvement after one month, the antipsychotic should be stopped.³ Addition of low doses of clomipramine may also be useful in some patients, although careful monitoring of adverse effects and ECG results may be warranted with such a combination.¹ Patients with severe and treatment-refractory OCD may be referred to specialised sites for deep brain stimulation or ablative neurosurgery, although this is rarely indicated.¹¹

For patients who do not respond to the initial SSRI, a different SSRI should be considered.¹¹ Although the chance of successful treatment is less with each switch to another SSRI after previous treatment failure, around one-third of patients respond to a new SSRI.¹ Patients who do not respond to treatment with one or more SSRIs may be considered for a trial of clomipramine.¹ In some cases, venlafaxine or a classic monoamine oxidase inhibitor have been effective in treatment-resistant OCD.¹

If initial treatment with CBT in children has failed, a medication trial with a suitable SSRI should be considered. (See Table 2.)

Table 3 provides several options for medication trials in patients with refractory OCD. The order of medication choice may be adapted to suit individual patients.³

Medicine Safety and Adverse Effects

SSRIs are considered first-line pharmacotherapy based on an overall better safety profile compared to clomipramine.^1-5 Adverse events with SSRIs are typically dose-dependent and transient.⁵ Sexual side-effects may be limited by reducing the dose where possible, encouraging a weekly one-day break from the medication before sexual activity, switching to another SSRI or adding a pharmacologic agent such as bupropion.¹¹

Although controversy exists around the relationship between suicidality and SSRI use in children, there seems to be a small increased risk of suicidal thoughts and behaviours, but not completed suicides.⁵ Younger children (10-14 years) on SSRIs are also at greater risk of developing mania when compared to adolescents and young adults.⁵

Clomipramine can cause anticholinergic adverse effects and some patients may not be able to tolerate these effects.^3,5

Addition of low doses of clomipramine to a SSRI requires careful monitoring of adverse effects and electrocardiograms (ECGs) may be warranted with this combination.¹ Patients should also be screened for cardiovascular disease before starting clomipramine and a follow-up ECG is recommended once patients have achieved a stable therapeutic dose and with each dose increase after that.⁵ Using higher doses of clomipramine with SSRIs can markedly increase clomipramine plasma drug levels, and although plasma drug levels do not correlate with dose, testing may be required to monitor for possible toxicity.^1,3,5 Patients taking clomipramine should avoid grapefruit and grapefruit juice as this may also increase clomipramine mean plasma levels.⁵

Concerns around metabolic side-effects with atypical antipsychotics exist, particularly in pre-adolescents who are more sensitive to weight gain, carbohydrate abnormalities and diabetes.⁵ Table 4 provides a summary of the most common adverse effects reported with pharmacotherapy in adults and children respectively.

Novel treatment options for OCD

The role of glutamatergic abnormalities has led to investigation into the use of glutamatergic treatment options for OCD.⁴ Although drugs such as riluzole, N-acetylcysteine, memantine and D-cycloserine have been studied in children, results thus far have been conflicting and evidence to support their use is limited.⁵ The same is true for the use of lithium, buspirone, clonazepam, L-triiodothyronine, pindolol, ondansetron and desipramine in adults.³ The use of d-amphetamine or caffeine, pregabalin and lamotrigine has shown promise in adults, but further studies are required.³ There is no information on the use of lamotrigine for the treatment of OCD in children, but cases of severe rash associated with the medication have been reported including Stevens-Johnson syndrome, toxic epidermal necrolysis and rash-related death and the risk is greater in paediatric patients treated with lamotrigine.⁵ Limited studies in adults found that the addition of the atypical antipsychotic, aripiprazole with SSRIs or clomipramine, have shown significant decreases in OCD symptoms compared to placebo, but further studies are required.³

Conclusion

Approximately 50% of all cases of OCD start in childhood or adolescence and persist throughout a person's life, with symptoms waxing and waning.^6,7 Co-morbidity with other psychiatric conditions is often the rule, rather than the exception.⁶ Using SSRIs in the treatment of OCD have additional benefits as these agents are also effective in treating several depressive and anxiety disorders associated with OCD. Only around 5% of patients will achieve full remission between exacerbations.⁴

A strong treatment alliance between the treating doctor, the patient with his/her family members, significant contacts, and other healthcare providers, is essential to increase the chances of successful treatment of OCD.¹¹

References:

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   3. Simpson HB. Pharmacotherapy for obsessive-compulsive disorder in adults. UpToDate. www.uptodate.com c2016 [cited 12 December 2019; updated 21 January 2015].
   4. Greenberg WM. Obsessive-compulsive disorder. Medscape. [cited 12 December 2019; updated 17 May 2018]. Available from https://emedicine.medscape.com/article/1934139-overview#showall
   5. Rosenberg D. Treatment of obsessive-compulsive disorder in children and adolescents. UpToDate. www.uptodate.com c2019 [cited 12 December 2019; updated 27 June 2019].
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   8. Storch EA, Benito K, Goodman W. Assessment scales for obsessive-compulsive disorder. Neuropsychiatry 2011;1 (3):243-250.
   9. LeBeau RT, Mischel ER, Cols OM, et al. Preliminary assessment of obsessive-compulsive spectrum disorder scales for DSM-5. Journal of Obsessive-Compulsive and Related Disorders 2013;2:114-118.
   10. Stein BM. Obsessive Compulsive disorder in pregnant and postpartum women. UpToDate. www.uptodate.com c2019 [cited 12 December 2019; updated 22 March 2018].
   11. Lambert M. Practice Guidelines. APA Releases Guidelines on treating obsessive-compulsive disorder. Am Fam Physician 2008 July 1;78(1):131-135. Cited: 12 December 2019. Available from: http://www.aafp.org/afp/2008/0701/p131.html
   12. Rossiter D. South African Medicines Formulary. 12th Edition. University of Cape Town, South Africa. Health and Medical Publishing Group. 2016;495-502.
   13. Anxiety BC. Obsessive Compulsive Disorder. Cited 12 December 2019. Available from https://www.anxietybc.com/parenting/obsessive-compulsive-disorder